Ophthalmology Commons^™

Fundus Autofluorescence Imaging: Fundamentals And Clinical Relevance., Yasir J. Sepah, Abeer Akhtar, Mohammad Ali Sadiq, Yamama Hafeez, Humzah Nasir, Brian Perez, Narissa Mawji, Diana J. Dean, Daniel Ferraz, Quan Dong Nguyen

Journal Articles: Ophthalmology

Fundus autofluorescence (FAF), a relatively new imaging modality, focuses on the fluorescent properties of pigments in the retina to generate images that help us view various disease processes from a different perspective. It aids us in the understanding of the pathophysiology of different retinal disorders. Recently, FAF imaging is being used commonly to help us in the diagnosis, prognosis as well as in determining the treatment response of various retinal disorders. It generates an image based on the distribution pattern of a fluorescent pigment called lipofuscin. Knowing the distribution pattern of lipofuscin in the normal retina is key to understanding …

Retina-Simulating Phantom For Optical Coherence Tomography., Jigesh Baxi, William Calhoun, Yasir Jamal Sepah, Daniel X. Hammer, Ilko Ilev, T. Joshua Pfefer, Quan Dong Nguyen, Anant Agrawal

Journal Articles: Ophthalmology

Optical coherence tomography (OCT) is a rapidly growing imaging modality, particularly in the field of ophthalmology. Accurate early diagnosis of diseases requires consistent and validated imaging performance. In contrast to more well-established medical imaging modalities, no standardized test methods currently exist for OCT quality assurance. We developed a retinal phantom which mimics the thickness and near-infrared optical properties of each anatomical retinal layer as well as the surface topography of the foveal pit. The fabrication process involves layer-by-layer spin coating of nanoparticle-embedded silicone films followed by laser micro-etching to modify the surface topography. The thickness of each layer and dimensions …

Emerging Therapies For Noninfectious Uveitis: What May Be Coming To The Clinics., Jose R. Maya, Mohammad A. Sadiq, Liz J. Zapata, Mostafa Hanout, Salman Sarwar, Nithya Rajagopalan, Kathleen E. Guinn, Yasir J. Sepah, Quan Dong Nguyen

Journal Articles: Ophthalmology

Corticosteroids along with other immunomodulatory therapies remain as the mainstay of treatment tor all patients with noninfectious uveitis (NIU). However, the systemic side effects associated with the long-term use of these drugs has encouraged the development of new therapeutic agents in recent times. This review article discusses upcoming therapeutic agents and drug delivery systems that are currently being used to treat patients with NIU. These agents mediate their actions by blocking specific pathways involved in the inflammatory process. Agents discussed in this review include full or recombinant monoclonal antibodies against interleukins such as IL-17 (secukinumab), IL-l (gevokizumab), and IL-6 (tocilizumab …

Surgery For Post-Vitrectomy Cataract, Diana V. Do, Stephen Gichuhi, Satyanarayana S. Vedula, Barbara S. Hawkins

Journal Articles: Ophthalmology

BACKGROUND: Cataract formation or acceleration can occur after intraocular surgery, especially following vitrectomy, a surgical technique for removing the vitreous which is used in the treatment of disorders that affect the posterior segment of the eye. The underlying problem that led to vitrectomy may limit the benefit from cataract surgery.

OBJECTIVES: The objective of this review was to evaluate the effectiveness and safety of surgery for post-vitrectomy cataract with respect to visual acuity, quality of life, and other outcomes.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 4), …

Long-Term Outcomes Of Ranibizumab Therapy For Diabetic Macular Edema: The 36-Month Results From Two Phase Iii Trials: Rise And Ride., David M. Brown, Quan Dong Nguyen, Dennis M. Marcus, David S. Boyer, Sunil Patel, Leonard Feiner, Patricio G. Schlottmann, Amy Chen Rundle, Jiameng Zhang, Roman G. Rubio, Anthony P. Adamis, Jason S. Ehrlich, J. Jill Hopkins

Journal Articles: Ophthalmology

PURPOSE: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME).

DESIGN: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years.

PARTICIPANTS: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography.

METHODS: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser …

Longitudinal Spectral Domain Optical Coherence Tomography Changes In Eyes With Intraocular Lymphoma, Hyun Soo Jang, Yasir J. Sepah, Raafay Sophie, Millena G. Bittencourt, Daniel Ferraz, Mostafa Hanout, Hongting Liu, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND:

Cases of patients with primary intraocular lymphoma (PIOL) were retrospectively analyzed to describe the longitudinal intra-retinal morphological changes in PIOL as visualized on images obtained by spectral domain optical coherence tomography (SD-OCT).

RESULTS:

In a retrospective case series, Heidelberg Spectralis SD-OCT images obtained in the longitudinal evaluation of patients with biopsy-proven PIOL were analyzed and assessed. The images were graded for the presence of macular edema (ME), pigment epithelial detachment (PED), subretinal fluid (SRF), and hyperreflective signals. SD-OCT scans of five eyes from five patients were assessed. Patients showed signs of inflammation, such as ME and SRF, which were …

Reliability And Reproducibility Of Spectral And Time Domain Optical Coherence Tomography Images Before And After Correction For Patients With Age-Related Macular Degeneration., Mohammad A. Sadiq, Aymen Rashid, Roomasa Channa, Elham Hatef, Diana V. Do, Quan Dong Nguyen, Yasir J. Sepah

Journal Articles: Ophthalmology

PURPOSE: To evaluate the reproducibility and reliability of optical coherence tomography scans obtained using the time domain (TD-OCT) Stratus (TM) OCT, and the Spectral Domain (SD-OCT) Spectralis (TM) and Cirrus (TM) OCT devices before and after manual correction in eyes with either Neovascular (NV-AMD) or Non-Neovascular (NNV-AMD) age-related macular degeneration.

DESIGN: Prospective observational study.

SETTING: University-based retina practice.

PATIENTS: Thirty-six patients (50 eyes) with NV-AMD or NNV-AMD.

PROCEDURE: OCT scans were taken simultaneously using one TD-OCT and two SD-OCT devices.

MAIN OUTCOME MEASURES: Macular thickness measurements were assessed before and after correction of the algorithm by constructing Bland-Altman plots for …

Corticosteroids As Adjuvant Therapy For Ocular Toxoplasmosis., Smitha Jasper, Satyanarayana S. Vedula, Sheeja S. John, Saban Horo, Yasir J. Sepah, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Ocular infestation with Toxoplasma gondii, a parasite, may result in inflammation in the retina, choroid, and uvea and consequently lead to complications such as glaucoma, cataract, and posterior synechiae.

OBJECTIVES: The objective of this systematic review was to assess the effects of adjunctive use of corticosteroids for ocular toxoplasmosis.

SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean …

Ocular Tolerability And Efficacy Of Intravitreal And Subconjunctival Injections Of Sirolimus In Patients With Non-Infectious Uveitis: Primary 6-Month Results Of The Save Study., Quan Dong Nguyen, Mohamed A. Ibrahim, Anthony Watters, Millena Bittencourt, Jithin Yohannan, Yasir J. Sepah, James P. Dunn, Joel Naor, Naveed Shams, Ovais Shaikh, Henry Alexander Leder, Diana V. Do

Journal Articles: Ophthalmology

BACKGROUND: The purpose of this study is to evaluate the ocular tolerability and efficacy of sirolimus administered as subconjunctival or intravitreal injections in patients with non-infectious uveitis. Sirolimus as a Therapeutic Approach for Uveitis (SAVE) is a prospective, randomized, open-label, interventional study. Thirty patients were enrolled and randomized in 1:1 ratio to receive either intravitreal injections of 352 μg sirolimus or subconjunctival injections of 1,320 μg at days 0, 60, and 120, with primary endpoint at month 6.

RESULTS: At month 6, all subjects with active uveitis at baseline showed reduction in vitreous haze of one or more steps. Forty …

Ultra-Wide-Field Retinal Imaging In The Management Of Non-Infectious Retinal Vasculitis., Henry A. Leder, John P. Campbell, Yasir J. Sepah, Theresa Gan, James P. Dunn, Elham Hatef, Brian Cho, Mohamed Ibrahim, Millena Bittencourt, Roomasa Channa, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: The purpose of this study is to describe and quantify the benefit of ultra-wide-field imaging and fluorescein angiography (FA) in the management of non-infectious retinal vasculitis. In this prospective observational cohort series, patients with non-infectious retinal vasculitis were evaluated and enrolled by four investigators from the Divisions of Retina and Ocular Immunology at the Wilmer Eye Institute. In each patient, disease activity and the need for management changes were assessed, based on clinical examination with or without standard (60°) imaging and then with the addition of ultra-wide-field pseudo-color scanning laser ophthalmoscope (SLO) images and FA using the Optos ultra-wide-field …

Lateral Mobility Of L-Type Calcium Channels In Synaptic Terminals Of Retinal Bipolar Cells., Wallace B. Thoreson, Aaron J. Mercer, Karlene M. Cork, Robert J. Szalewski

Journal Articles: Ophthalmology

PURPOSE: Efficient and precise release of glutamate from retinal bipolar cells is ensured by the positioning of L-type Ca(2+) channels close to release sites at the base of the synaptic ribbon. We investigated whether Ca(2+) channels at bipolar cell ribbon synapses are fixed in position or capable of moving in the membrane.

METHODS: We tracked the movements of individual L-type Ca(2+) channels in bipolar cell terminals after labeling channels with quantum dots (QDs) attached to α(2)δ(4) accessory Ca(2+) channel subunits via intermediary antibodies.

RESULTS: We found that individual Ca(2+) channels moved within a confined domain of 0.13-0.15 μm(2) in bipolar …

Therapies For Neovascular Age-Related Macular Degeneration: Current Approaches And Pharmacologic Agents In Development., Mostafa Hanout, Daniel Ferraz, Mehreen Ansari, Natasha Maqsood, Saleema Kherani, Yasir J. Sepah, Nithya Rajagopalan, Mohamed Ibrahim, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

As one of the leading causes of blindness, age-related macular degeneration (AMD) has remained at the epicenter of clinical research in ophthalmology. During the past decade, focus of researchers has ranged from understanding the role of vascular endothelial growth factor (VEGF) in the angiogenic cascades to developing new therapies for retinal vascular diseases. Anti-VEGF agents such as ranibizumab and aflibercept are becoming increasingly well-established therapies and have replaced earlier approaches such as laser photocoagulation or photodynamic therapy. Many other new therapeutic agents, which are in the early phase clinical trials, have shown promising results. The purpose of this paper is …

Vascular Disrupting Agent For Neovascular Age Related Macular Degeneration: A Pilot Study Of The Safety And Efficacy Of Intravenous Combretastatin A-4 Phosphate, Mohamed A. Ibrahim, Diana V. Do, Yasir J. Sepah, Syed M. Shah, Elizabeth Van Anden, Gulnar Hafiz, J. Kevin Donahue, Richard Rivers, Jai Balkissoon, James T. Handa, Peter A. Campochiaro, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND:

This study was designed to assess the safety, tolerability, and efficacy of intravenous infusion of CA4P in patients with neovascular age-related macular degeneration (AMD).

METHODS:

Prospective, interventional, dose-escalation clinical trial. Eight patients with neovascular AMD refractory to at least 2 sessions of photodynamic therapy received CA4P at a dose of 27 or 36 mg/m2 as weekly intravenous infusion for 4 consecutive weeks. Safety was monitored by vital signs, ocular and physical examinations, electrocardiogram, routine laboratory tests, and collection of adverse events. Efficacy was assessed using retinal fluorescein angiography, optical coherence tomography, and best corrected visual acuity (BCVA).

RESULTS:

The …

Rapid Synaptic Vesicle Endocytosis In Cone Photoreceptors Of Salamander Retina., Matthew J. Van Hook, Wallace B. Thoreson

Journal Articles: Ophthalmology

Following synaptic vesicle exocytosis, neurons retrieve the fused membrane by a process of endocytosis to provide a supply of vesicles for subsequent release and maintain the presynaptic active zone. Rod and cone photoreceptors use a specialized structure called the synaptic ribbon that enables them to sustain high rates of neurotransmitter release. They must also employ mechanisms of synaptic vesicle endocytosis capable of keeping up with release. While much is known about endocytosis at another retinal ribbon synapse, that of the goldfish Mb1 bipolar cell, less is known about endocytosis in photoreceptors. We used capacitance recording techniques to measure vesicle membrane …

Evaluation Of Very High- And Very Low-Dose Intravitreal Aflibercept In Patients With Neovascular Age-Related Macular Degeneration., Quan Dong Nguyen, Peter A. Campochiaro, Syed Mahmood Shah, David J. Browning, Henry L. Hudson, Peter L. Sonkin, Seenu M. Hariprasad, Peter K. Kaiser, Jason Slakter, Julia A. Haller, Diana V. Do, William Mieler, Karen Chu, Avner Ingerman, Robert Vitti, Alyson J. Berliner, Jesse Cedarbaum, Clear-It 1 Investigators

Journal Articles: Ophthalmology

PURPOSE: To determine bioactivity and duration of effect of intravitreal aflibercept injection (also known as vascular endothelial growth factor Trap-Eye) for neovascular age-related macular degeneration (AMD).

METHODS: In this double-masked, phase 1 study, 28 patients with lesions ≤12 disc areas, ≥50% active choroidal neovascularization (CNV), and best corrected visual acuity (BCVA) ≤20/40 were randomized 1:1 to a single intravitreal injection of aflibercept 0.15 or 4 mg. The primary end point was the change from baseline in central retinal/lesion thickness (CR/LT) at week-8. Secondary outcomes were the change from baseline BCVA, the change in CNV lesion size and area of leakage, …

Retinal Optical Coherence Tomography Manifestations Of Intraocular Lymphoma., Tin Yan Alvin Liu, Mohamed Ibrahim, Millena Bittencourt, Yasir J. Sepah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

PURPOSE: Primary central nervous system lymphoma (PCNSL) is a rare disease. The index report describes a patient with intraocular lymphoma secondary to recurrent PCNSL and corresponding retinal findings on spectral domain optical coherence tomography (SD-OCT).

METHODS: Case report.

RESULTS: OCT changes were documented and correlated with the clinical course of intraocular lymphoma progression in the index patient. The OCT changes, manifested as hyperreflective material accumulation in the intraretinal and subretinal pigment epithelial spaces, were caused by lymphomatous infiltration.

CONCLUSION: SD-OCT can be useful in diagnosing and monitoring the progression or regression of intraocular lymphoma with retinal involvement.

Nucleic Acid And Non-Nucleic Acid-Based Reprogramming Of Adult Limbal Progenitors To Pluripotency, Sowmya Parameswaran, Sudha Balasubramanian, Norbert Babai, Carolina B. Deldebbio, Donald W. Harms, Channabasavaiah B. Gurumurthy, Mahendra S. Rao, J. Graham Sharp, Iqbal Ahmad

Journal Articles: Ophthalmology

Reprogramming somatic cells to a pluripotent state by nucleic acid based (NAB) approaches, involving the ectopic expression of transcription factors, has emerged as a standard method. We recently demonstrated that limbal progenitors that regenerate cornea are reprogrammable to pluripotency by a non-NAB approach through simple manipulation of microenvironment thus extending the possible therapeutic use of these readily accessible cells beyond the proven treatment of corneal diseases and injury. Therefore, to determine the validity and robustness of non-cell autonomous reprogramming of limbal progenitors for a wider clinical use, here, we have compared their reprogramming by non-NAB and NAB approaches. We observed …

Choroidal Neovascularization Regression On Fluorescein Angiography After Vegf Blockade., Diana V. Do, Lark Greenwald, Mohamed Ibrahim, Yasir J. Sepah, Quan Dong Nguyen

Journal Articles: Ophthalmology

BACKGROUND: Intravitreal vascular endothelial growth factor (VEGF) inhibitors stabilize vision in a majority of patients with neovascular age-related macular degeneration (AMD) and can improve vision in almost 40% of patients. However, some individuals who respond to anti-VEGF treatment still lose vision due to the formation of geographic atrophy (GA). While optical coherence tomography is often the primary imaging modality used, fluorescein angiography (FA) can provide useful information on GA development after choroidal neovascularization (CNV) regression.

METHODS: A retrospective chart review was conducted to evaluate the changes seen on FA over a 47-month period for 3 patients with neovascular AMD treated …

Characterization Of Macular Lesions In Punctate Inner Choroidopathy With Spectral Domain Optical Coherence Tomography., Roomasa Channa, Mohamed Ibrahim, Yasir J. Sepah, Peykan Turkcuoglu, Jeong Hee Lee, Afsheen Khwaja, Elham Hatef, Millena Bittencourt, Jangwon Heo, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

PURPOSE: Punctate inner choroidopathy (PIC) is an ocular inflammatory disease. Spectral domain optical coherence tomography (SD-OCT) allows detailed visualization of retinal and choroidal structures. We aimed to describe the retinal changes on SD-OCT associated with PIC lesions localized in the macula.

METHODS: Retrospective case series: PIC lesions not associated with choroidal neovascularization (CNV) and captured by macular SD-OCT scans were identified and characterized.

RESULTS: Twenty-seven PIC lesions from seven patients (eight eyes) were identified and classified into four categories according to disease activity and temporal changes. Among clinically inactive patients, two main patterns were noted on OCT: (1) retinal pigment …

Isolated Endogenous Nocardia Endophthalmitis After Immunosuppression., Lisa Y. Chen, Muge R. Kesen, Abdalhossein Ghafourian, Quan Dong Nguyen, Charles G. Eberhart, Diana V. Do

Journal Articles: Ophthalmology

PURPOSE: This study is aimed to report a case of endogenous Nocardia endophthalmitis in the setting of immunosuppression from chronic steroid use.

METHODS: A case report was conducted.

RESULTS: A 79-year-old woman presented with decreased vision with floaters in the left eye. Ophthalmic examination revealed severe inflammation in the anterior chamber, vitreous opacities, and retinal detachment. Vitreous cultures grew Nocardia farcinica without any systemic foci of infection found during further workup. The patient was treated with intravitreal amikacin and oral trimethoprim-sulfamethoxazole, and her retinal detachment was later repaired in the operating room. The patient has since remained stable with no …

Macular Sensitivity And Fixation Patterns In Normal Eyes And Eyes With Uveitis With And Without Macular Edema., Yasir J. Sepah, Elham Hatef, Elizabeth Colantuoni, Jianmin Wang, Mathew Shulman, Fatima I. Adhi, Abeer Akhtar, Mohamed Ibrahim, Afsheen Khwaja, Roomasa Channa, Raafay Sophie, Millena Bittencourt, Jangwon Heo, Diana V Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

PURPOSE: This study aims to investigate the relationship between macular sensitivity and thickness in eyes with uveitic macular edema (UME).

DESIGN: This study is a prospective observational case series.

METHODS: The setting for this study was clinical practice. The study included 59 (28 with UME, 31 without UME) eyes of 26 patients with uveitis and 19 eyes of 10 normal subjects. The procedure followed was fundus-related perimetry and retinal thickness map with an automated fundus perimetry/tomography system. Main outcome measures included quantification of macular sensitivity, fixation pattern, and relationship between macular sensitivity and thickness.

RESULTS: Fixation stability revealed that 56 …

Hospitalized Cardiovascular Events In Patients With Diabetic Macular Edema., Bao-Anh Nguyen-Khoa, Earl L. Goehring, Winifred Werther, Anne E. Fung, Diana V. Do, Rajendra S. Apte, Judith K. Jones

Journal Articles: Ophthalmology

BACKGROUND: Microvascular and macrovascular complications in diabetes stem from chronic hyperglycemia and are thought to have overlapping pathophysiology. The aim of this study was to investigate the incidence rate of hospitalized myocardial infarctions (MI) and cerebrovascular accidents (CVA) in patients with diabetic macular edema (DME) compared with diabetic patients without retinal diseases.

METHODS: This was a retrospective cohort study of a commercially insured population in an administrative claims database. DME subjects (n = 3519) and diabetes controls without retinal disease (n = 10557) were matched by age and gender. Healthcare claims were analyzed for the study period from 1 January …

Comparison Of Time Domain And Spectral Domain Optical Coherence Tomography In Measurement Of Macular Thickness In Macular Edema Secondary To Diabetic Retinopathy And Retinal Vein Occlusion., Elham Hatef, Afsheen Khwaja, Zubir Rentiya, Mohamed Ibrahim, Matthew Shulman, Peykan Turkcuoglu, Yasir J. Sepah, Jianmin Wang, Roomasa Channa, Millena Bittencourt, Abeer Akhtar, Jangwon Heo, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

Purpose. To evaluate macular thickness, agreement, and intraclass repeatability in three optical coherence tomography (OCT) devices: the time domain (TD) Stratus OCT and two spectral domain (SD) OCTs, Spectralis and Cirrus SD-OCT, in eyes with macular edema secondary to diabetic retinopathy (DR) and retinal vein occlusion (VO). Methods. In a prospective observational study at a university-based retina practice, retinal thickness tomography was performed simultaneously for fifty-eight patients (91 eyes) with DR and VO employing a time domain and two spectral domain OCTs. Agreement in macular measurements was assessed by constructing Bland-Altman plots. Intraclass repeatability was assessed by intraclass correlation coefficients …

Post-Cataract Outcomes In Patients With Noninfectious Posterior Uveitis Treated With The Fluocinolone Acetonide Intravitreal Implant., John D. Sheppard, Quan Dong Nguyen, Dale W. Usner, Timothy L. Comstock

Journal Articles: Ophthalmology

PURPOSE: To describe visual acuity (VA) and inflammation following cataract surgery in eyes with noninfectious posterior uveitis (NIPU) that were being treated with a fluocinolone acetonide (FA) intravitreal implant compared with those that were not.

DESIGN: Post hoc, subgroup analysis of data from a 3-year, dose-masked, randomized, multicenter trial evaluating the FA implant for the treatment of NIPU.

PARTICIPANTS AND CONTROLS: The subset of eyes that underwent cataract surgery during the 3-year trial. Eyes were either implanted with a 0.59- or a 2.1-mg FA implant, or, in the case of affected fellow eyes, received standard-of-care local treatment.

MAIN OUTCOME MEASURES: …

Importance Of Proper Diagnosis For Management: Multifocal Choroiditis Mimicking Ocular Histoplasmosis Syndrome., Elham Hatef, Peykan Turkcuoglu, Mohamed Ibrahim, Yasir J. Sepah, Matthew Shulman, Jangwon Heo, Jeong H. Lee, Roomasa Channa, Afsheen Khwaja, Zubir Rentiya, Syed Mahmood Shah, Diana V. Do, Quan Dong Nguyen

Journal Articles: Ophthalmology

PURPOSE: The study aims to evaluate a series of patients with initial diagnosis of ocular histoplasmosis syndrome (OHS) with progression and response to treatments consistent with multifocal choroiditis (MFC).

METHODS: Retrospective review of nine patients referred for management of recurrent OHS lesions. Serology panel was conducted to rule out autoimmune and infectious causes.

RESULTS: Clinical examination revealed multiple small, punched-out peripheral chorioretinal scars, and peripapillary atrophy. Histoplasma antigen/antibody was negative in all patients. Fluorescein angiography and optical coherence tomography confirmed active inflammation in five patients. Immunomodulatory therapy (IMT) was initiated to control active inflammation. While on IMT, visual acuity stabilized …

A Positive Feedback Synapse From Retinal Horizontal Cells To Cone Photoreceptors., Skyler L. Jackman, Norbert Babai, James J. Chambers, Wallace B. Thoreson, Richard H. Kramer

Journal Articles: Ophthalmology

Cone photoreceptors and horizontal cells (HCs) have a reciprocal synapse that underlies lateral inhibition and establishes the antagonistic center-surround organization of the visual system. Cones transmit to HCs through an excitatory synapse and HCs feed back to cones through an inhibitory synapse. Here we report that HCs also transmit to cone terminals a positive feedback signal that elevates intracellular Ca(2+) and accelerates neurotransmitter release. Positive and negative feedback are both initiated by AMPA receptors on HCs, but positive feedback appears to be mediated by a change in HC Ca(2+), whereas negative feedback is mediated by a change in HC membrane …

Quantal Amplitude At The Cone Ribbon Synapse Can Be Adjusted By Changes In Cytosolic Glutamate., Theodore M. Bartoletti, Wallace B. Thoreson

Journal Articles: Ophthalmology

PURPOSE: Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles.

METHODS: We introduced glutamate (10-40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation.

RESULTS: Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate …

Lateral Mobility Of Presynaptic L-Type Calcium Channels At Photoreceptor Ribbon Synapses., Aaron J. Mercer, Minghui Chen, Wallace B. Thoreson

Journal Articles: Ophthalmology

At most synapses, presynaptic Ca(2+) channels are positioned near vesicle release sites, and increasing this distance reduces synaptic strength. We examined the lateral membrane mobility of presynaptic L-type Ca(2+) channels at photoreceptor ribbon synapses of the tiger salamander (Ambystoma tigrinum) retina. Movements of individual Ca(2+) channels were tracked by coupling quantum dots to an antibody against the extracellular α(2)δ(4) Ca(2+) channel subunit. α(2)δ(4) antibodies labeled photoreceptor terminals and colocalized with antibodies to synaptic vesicle glycoprotein 2 and voltage-gated Ca(2+) channel 1.4 (Ca(V)1.4) α(1) subunits. The results show that Ca(2+) channels are dynamic and move within a confined region beneath the …

Calcium Regulates Vesicle Replenishment At The Cone Ribbon Synapse., Norbert Babai, Theodore M. Bartoletti, Wallace B. Thoreson

Journal Articles: Ophthalmology

Cones release glutamate-filled vesicles continuously in darkness, and changing illumination modulates this release. Because sustained release in darkness is governed by vesicle replenishment rates, we analyzed how cone membrane potential regulates replenishment. Synaptic release from cones was measured by recording postsynaptic currents in Ambystoma tigrinum horizontal or OFF bipolar cells evoked by depolarization of simultaneously voltage-clamped cones. We measured replenishment after attaining a steady state between vesicle release and replenishment using trains of test pulses. Increasing Ca(2+) currents (I(Ca)) by changing the test step from -30 to -10 mV increased replenishment. Lengthening -30 mV test pulses to match the Ca(2+) …

Anion-Sensitive Regions Of L-Type Cav1.2 Calcium Channels Expressed In Hek293 Cells., Norbert Babai, Nataly Kanevsky, Nathan Dascal, George J. Rozanski, Dhirendra P. Singh, Nigar Fatma, Wallace B. Thoreson

Journal Articles: Ophthalmology

L-type calcium currents (I(Ca)) are influenced by changes in extracellular chloride, but sites of anion effects have not been identified. Our experiments showed that CaV1.2 currents expressed in HEK293 cells are strongly inhibited by replacing extracellular chloride with gluconate or perchlorate. Variance-mean analysis of I(Ca) and cell-attached patch single channel recordings indicate that gluconate-induced inhibition is due to intracellular anion effects on Ca(2+) channel open probability, not conductance. Inhibition of CaV1.2 currents produced by replacing chloride with gluconate was reduced from approximately 75%-80% to approximately 50% by omitting beta subunits but unaffected by omitting alpha(2)delta subunits. Similarly, gluconate inhibition was …